Systems and methods for sensing lung fluid and functionality

ABSTRACT

An apparatus for monitoring for accumulation of lung fluid comprises a feeding tube having first electrode(s) positioned thereon for electrical contact with tissue of an esophagus of a target patient including a lower esophageal sphincter (LES) and/or tissue in proximity to the LES, second electrode(s) sized and shaped for contacting skin of the target patient, and a non-transitory memory having stored thereon code instructions for applying alternating current(s) to pair(s) of first and second electrodes, measuring a voltage over the pair(s), and computing an estimate of a change of lung fluid relative to a baseline in lung(s) of the target patient according to the applied alternating current and measured voltage, wherein the applying, the measuring, and the computing the estimate of the change in lung fluid are iteratively executed for monitoring the target patient for accumulation of lung fluid while the feeding tube is in use.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/095,832 filed on Nov. 12, 2020, which is a continuation of U.S.patent application Ser. No. 16/467,078 filed on Jun. 6, 2019, now U.S.Pat. No. 10,835,178, which is a National Phase of PCT Patent ApplicationNo. PCT/IB2017/057702 having International Filing Date of Dec. 6, 2017,which claims the benefit of priority under 35 USC § 119(e) of U.S.Provisional Patent Application No. 62/430,378 filed on Dec. 6, 2016.

The contents of the above applications are all incorporated by referenceas if fully set forth herein in their entirety.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates tointra-body fluid measurements and, more specifically, but notexclusively, to systems and methods for sensing lung fluid of a patient.

Pleural effusion is the collection of fluid outside the lungs, in thepleural space of the lungs. Pulmonary edema is the collection of fluidinside lungs, within the alveoli and/or parenchyma. Pleural effusionand/or pulmonary edema may present within patients, for example patientsadmitted to the intensive care unit (ICU), for example, as a saturationdrop.

Pleural effusion and pulmonary edema share some aspects ofpathophysiology, for example, resulting from cardiac failure, fluidoverload, liver failure, and/or renal failure. For example, failure ofthe left ventricle of the heart to adequately remove blood from thepulmonary circulation, and/or an injury to the lung parenchyma orvasculature of the lung.

Pulmonary edema leads to airway obstruction and respiratory failure.There are two recognized types of Pulmonary edema:

Type I follows a sudden, severe episode of upper airway obstruction(such as post-extubation laryngospasm) and may be associated with anycause of acute airway obstruction.

Type II develops after surgical relief of chronic upper airwayobstruction. The incidence of development of pulmonary edema in acuteupper airway obstruction (type I) ranges from 9.6-12% and that inchronic airway obstruction (type II) is 44%. Morbidity and mortalityrates range from 11% to 40%.

SUMMARY OF THE INVENTION

According to a first aspect, an apparatus for monitoring a targetpatient for accumulation of lung fluid, the apparatus comprises: afeeding tube for insertion into a distal end of an esophagus of thetarget patient, at least one first electrode disposed on the distal endof the feeding tube at a location such that the at least one firstelectrode is located at the distal end of the esophagus of the targetpatient when the feeding tube is located within the esophagus and in useand, wherein the at least one first electrode is positioned forelectrical contact with the tissue of the esophagus including at leastone of a lower esophageal sphincter (LES) and tissue in proximity to theLES, at least one second electrode sized and shaped for contacting thesurface of the skin of the target patient, and a non-transitory memoryhaving stored thereon a code for execution by at least one hardwareprocessor of a computing device, the code including instruction forapplying at least one alternating current to at least one pair of firstand second electrodes, measuring a voltage over the at least one pair offirst and second electrodes, and computing an estimate of a change oflung fluid relative to a baseline in at least one lung of the targetpatient according to the applied alternating current and measuredvoltage, wherein the applying the at least one alternating current, themeasuring the voltage drop, and the computing the estimate of the changein lung fluid are iteratively executed for monitoring the target patientfor accumulation of lung fluid while the feeding tube is in use.

According to a second aspect, a method for sensing lung fluid of atarget patient, the method comprises: applying at least one alternatingcurrent to at least one first electrode, wherein the at least one firstelectrode is disposed on a distal end of an feeding tube sized andshaped for insertion into a distal end of an esophagus of the targetpatient, at a location such that the at least one first electrode islocated at the distal end of the esophagus of the target patient whenthe feeding tube is located within the esophagus and in use, wherein theat least one first electrode is positioned for electrical contact withthe tissue of the esophagus including at least one of a lower esophagealsphincter (LES) and tissue in proximity to the LES, measuring a voltagedrop over at least one pair of a first and second electrode, wherein atleast one second electrode is sized and shaped for contacting thesurface of the skin of the target patient, and computing an estimate ofan change of lung fluid relative to a baseline in at least one lung ofthe target patient according to the applied alternating current and themeasured voltage drop, wherein the applying the at least one alternatingcurrent, the measuring the voltage drop, and the computing the estimateof the amount of fluid are iteratively executed for monitoring thetarget patient while the feeding tube is in use.

The systems, methods, apparatus, and/or code instructions describedherein relate to the technical problem of monitoring for accumulation oflung fluid. In particular, continuously (or near continuously, forexample, at closely spaced intervals, for example, every minute, 5minutes, or 10 minutes) monitoring the amount of lung fluid. Thetechnical problem may relate to monitoring for a clinically significantamount of lung fluid, and/or a prediction of a risk of developing aclinically significant amount of lung fluid. The clinically significantamount of lung fluid may affect the patient's breathing, and/or mayrequire treatment (e.g., drainage) and/or further investigation ofunderlying causes. Prediction of risk of impending accumulation ofclinically significant amount of lung fluid may trigger early treatmentto prevent the accumulation, for example, treatment of early heartfailure before the lung fluid accumulates.

The systems, methods, apparatus, and/or code instructions describedherein may relate to the technical problem of safety detecting lungfluid. In contrast, some other approaches are based on an electrodepositioned within or in proximity to the heart. When lung fluid ismeasured by these approaches, current is passed through the heart, whichincreases the risk of, for example, of an arrhythmia. In contrast, thesystems, methods, apparatus, and/or code instructions described hereinare based on locating sensor(s) away from the heart, optionally inproximity to the lower esophageal sphincter, which prevent passages ofelectrical current through the heart, or significantly reduce electricalcurrent through the heart to safe levels. Some other approaches arebased on electrodes located externally to the skin of the patient. Thecurrent applied between such electrodes may entirely bypass the lung, ormostly bypass the lung, resulting in inaccurate measurements that areunable to correctly sense the amount of lung fluid. In contrast, thesystems, methods, apparatus, and/or code instructions described hereinare based on sandwiching one or each lung between the electrodes, whichdirects most or all of the current

Some implementations of the systems, methods, apparatus, and/or codeinstructions described herein improve the performance of existing tubesand/or electrodes, which are positioned with the esophagus of thepatient for other reasons, for example, a nasogastric tube for removingfluid from the stomach and/or digestive system of the patient, and/or anenteral feeding tube for delivering enteral feedings to the stomachand/or digestive system of the patient. The impedance readings obtainedby the electrodes, which may be obtained for other reasons (e.g.,determine a reflux event, monitor correct positioning of the tube,and/or estimate amount of fluid in the stomach) may be further utilizedto monitor the patient for accumulation of lung fluid. The patient maybe monitored for accumulation of lung fluid while the tube and/orelectrodes are utilized for other purposes. For example, while anintubated patient is being enterally fed over a 24 period, the feedingtube is simultaneously utilized for monitoring for accumulation of lungfluid.

The systems, methods, apparatus, and/or code instructions describedherein do not simply perform automation of a manual procedure, butperform additional automated features which cannot be performed manuallyby a human using pencil and/or paper. According to current practice,detection of lung fluid is generally a medical art, based on thephysical performing one or more of the following: observation ofbreathing difficulty, detection of low oxygen saturation, auscultationof the lungs, analysis of a chest x-ray, and performing an analysis ofpleural fluid (which is obtained by a painful procedure in which aneedle is inserted into the pleural space). Lung fluid is more reliablydetected based on images acquired by advanced imaging modalities, forexample, computed tomography (CT) and magnetic resonance imaging (MRI),which however are not always available, and take time to analyze.Monitoring the development of lung fluid according to current practiceis difficult, and unreliable. Moreover, current methods are based onestimating existing lung fluid, and do not relate to prediction of riskof accumulation of lung fluid. In contrast, the systems, methods,apparatus, and/or code instructions described herein provide real-time,optionally continuous, monitoring of the amount of lung fluid, real-timedetection of accumulation of a clinically significant amount of lungfluid, and/or optionally predict a risk of accumulation of an excessamount of lung fluid in the near future. An indication of the monitoringand/or prediction is generated, which provides healthcare workers withearly and/or advanced notification for taking preventing action and/orearly treatment to avoid complications and/or consequences of delayeddiagnosis and treatment.

In a further implementation form of the first and second aspects, theapplying, the measuring, and the computing are continuously executed forcontinuous monitoring of the target patient for accumulation of lungfluid.

In a further implementation form of the first and second aspects, the atleast one first electrode is disposed on the distal end of the feedingtube at a location such that the at least one electrode is located atleast one of: in proximity to the LES and in contact with the LES of thetarget patient.

In a further implementation form of the first and second aspects, aplurality of second electrodes are placed on the skin of the targetindividual at locations corresponding to each of two lungs forindependent monitoring of lung fluid of each lung.

In a further implementation form of the first and second aspects, thefeeding tube includes an enteral feeding tube having a distal enddesigned for positioning within the digestive system when in use forenteral feeding.

In a further implementation form of the first and second aspects, thefeeding tube includes a nasogastric tube having a distal end designedfor positioning within the digestive system when in use.

In a further implementation form of the first and second aspects, the atleast one first electrode is associated with a clip-on attachmentmechanism that attaches to an off-the-shelf feeding tube.

In a further implementation form of the first and second aspects, thefeeding tube includes a catheter having at least one lumen that includeswires for transmission of signals between the at least one firstelectrode and an externally located at least one hardware processor.

In a further implementation form of the first and second aspects, the atleast one first electrode is mounted on an inflatable balloon located atthe distal end of the feeding tube, wherein when the inflatable balloonis inflated the at least one first electrode contacts the inner wall ofthe esophagus.

In a further implementation form of the first and second aspects, the atleast one first electrode and the at least one second electrode includeelectrodes for generating the at least one alternating current and forsensing the generated at least one alternating current.

In a further implementation form of the first and second aspects, the atleast one second electrode includes at least one pad electrode designedfor contacting the skin of the target patient.

In a further implementation form of the first and second aspects, thecomputing the estimate of the amount of lung fluid changes in at leastone lung of the target patient according to the applied alternatingcurrent is indicative of pulmonary edema at a certain lung lobe when theat least one second electrode is positioned on the skin of the targetpatient corresponding to the certain lung lobe.

In a further implementation form of the first and second aspects, thecomputing the estimate, based on initial base measurement of the changesof lung fluid in at least one lung of the target patient according tothe applied alternating current is indicative of pulmonary effusion of acertain lung when the at least one second electrode is positioned on theskin of the target patient corresponding to the base of the certainlung.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions fordifferentiating between pulmonary edema and pleural effusion accordingto an analysis of impedance values measured by at least one secondelectrode located on skin of the target individual corresponding to thebase of at least one lung and impedance values measured by another atleast one second electrode located on skin of the target individualcorresponding to one or more lobes of the at least one lung.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forestimating changes in level of fluid within the digestive system basedon an analysis of the applied alternating current and measured voltagedrop.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions formonitoring a position of the feeding tube within the digestive systembased on an analysis of the applied alternating current and measuredvoltage drop.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions fordetecting a gastric reflux event based on an analysis of the appliedalternating current and measured voltage drop and distinguishing thereflux event from lung fluid changes.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forestimating a change in lung function relative to a lung functionbaseline according to a correlation between change in lung fluid andlung function.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forcomparing lung fluid changes between the left and right lung fordifferentiation between lung fluid processes that affect both lungs fromlung fluid processes that affect one lung more than the other.

In a further implementation form of the first and second aspects, theamount of lung fluid is estimated for the left lung and right lung ofthe target patient according to measurements performed by a left set ofthe at least one second electrodes positioned on the left side of thetarget patient in proximity to the left lung and a right set of the atleast one second electrodes positioned on the right side of the targetpatient in proximity to the right lung and the same set of common atleast one first electrodes.

In a further implementation form of the first and second aspects, theestimated of an amount of lung fluid in at least one lung of the targetpatient is computed based on impedance values computed according to theapplied at least one alternating current and sensed voltage.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions formapping the impedance values to an indication of clinically significantamount of lung fluid.

In a further implementation form of the first and second aspects, theamount of lung fluid is estimated according to a reference set of basevalues measured from a plurality of sampled individuals that map betweenmeasured impedance values and amounts of lung fluids.

In a further implementation form of the first and second aspects, theamount of lung fluid is estimated by code for: computing at least oneimpedance value corresponding the at least one frequency of the at leastone applied current, converting the computed at least one impedancevalue to an impedance score associated with a time stamp indicative ofthe time of application of the at least one applied current, andpresenting the impedance score as a value on a graph within a graphicaluser interface (GUI) displayed on a display of a client terminal,wherein an x-axis of the graph denotes the time of application of the atleast one applied current and a y-axis of the graph denotes theimpedance score.

In a further implementation form of the first and second aspects, thegraph includes an indication of a threshold differentiating betweenclinically significant amount of fluid and clinically insignificantamount of fluid.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forcomputing the impedance score according to a member selected from thegroup consisting of: a real component of a complex impedance value, animaginary component of a complex impedance value, and a length of avector computed according to the real and complex components.

In a further implementation form of the first and second aspects, thegraph presented within the GUI includes a plurality of impedance scorescomputed over an interval of time, and further comprising code for:computing a trend line for at least a sub-set of recent impedancescores, and predicting an impending accumulation of a clinicallysignificant change in the amount of lung fluid according to an extensionof the trend line that crosses at a future time a thresholddifferentiating between clinically significant amount of fluid andclinically insignificant amount of fluid.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forpredicting a probability of impending accumulation of clinicallysignificant amount of lung fluid according to at least one of: acorrelation value indicative of fit of the trend line to the sub-set ofrecent impedance scores, and the amount of time in the future when thetrend line is predicted to reach the threshold.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions fordynamically computing the trend line by a least square best fit of aline to recent impedance scores within a sliding window, as newimpedance scores are plotted on the graph.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forcomputing a baseline impedance value indicative of a first amount offluid in the at least one lung denoted as clinically insignificant, andmonitoring measured impedance values to detect a drop in the impedancevalue below a threshold indicative of a second amount of fluid in the atleast one lung denoted as clinically significant.

In a further implementation form of the first and second aspects, thesystem and/or method further comprise code for and/or instructions forgenerating an alert when a set of rules is met indicative of animpending accumulation of clinically significant amount of lung fluidaccording to a defined risk threshold, and transmitting the alert forpresentation on at least one of: a client terminal, a mobile device, anda server.

In a further implementation form of the first and second aspects, aprobability of the impending accumulating of clinically significantamount of lung fluid is computed according to a direction of a trendline towards threshold denoting accumulation of clinically significantamount of fluid, the trend line computed based on a plurality ofimpedance values measured over a recent time interval.

In a further implementation form of the first and second aspects, thelung fluid includes at least one of: pleural effusion and lung edema.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example and for purposes of illustrativediscussion of embodiments of the invention. In this regard, thedescription taken with the drawings makes apparent to those skilled inthe art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a flowchart of a method for sensing lung fluid of a targetpatient based on at least one electrode positioned within the esophagusand/or stomach of a target patient, in accordance with some embodimentsof the present invention;

FIG. 2 is a schematic of components of a system for sensing lung fluidof a target patient based on at least one intra-body electrodepositioned within the esophagus and/or stomach of a target patient, inaccordance with some embodiments of the present invention;

FIG. 3 is a schematic depicting a dangerous set-up of measuring lungfluid based on other proposed approaches, to illustrate the safe set-upaccording to some embodiments of the present invention;

FIG. 4 is a schematic depicting a safe set-up of measuring lung fluidbased on an alternating current passing through the lung(s) whileavoiding passing through the heart, in accordance with some embodimentsof the present invention;

FIG. 5 is a schematic depicting an exemplary positioning of intra-bodyelectrode(s) and extracorporeal electrode(s) for sensing fluid in one ormore lungs of a target individual, in accordance with some embodimentsof the present invention;

FIG. 6 is a schematic depicting an electrical setup for measurement ofimpedance across a lung of target individual for sensing fluid withinthe lung, in accordance with some embodiments of the present invention;

FIG. 7 is a schematic depicting an abstract representation of theelectrical setup for measurement of impedance across a lung of targetindividual for sensing fluid within the lung, in accordance with someembodiments of the present invention;

FIG. 8 is a schematic of an environment set-up for sensing fluid withina lung(s) of a target patient based on an intra-body electrode(s)positioned along a feeding tube located within an esophagus of a targetindividual, in accordance with some embodiments of the presentinvention;

FIG. 9 is a schematic of an electronic measurement system for sensingfluid within one or more lungs of a patient based on at least oneintra-body electrode positioned within the esophagus in proximity to theLES, in accordance with some embodiments of the present invention;

FIG. 10 is an exemplary graph for analyzing the computed impedancevalue(s) for determining an indication of a clinically significantamount of excess fluid in the lungs, in accordance with some embodimentsof the present invention; and

FIG. 11 is a schematic of an exemplary graph presented on a displayindicative of the sensed lung fluid, in accordance with some embodimentsof the present invention; and

FIG. 12 is a schematic depicting an exemplary computed lung functionand/or lung fluid map for presentation on a display of a client terminal(e.g., within a GUI), in accordance with some embodiments of the presentinvention.

DETAILED DESCRIPTION

The present invention, in some embodiments thereof, relates tointra-body fluid measurements and, more specifically, but notexclusively, to systems and methods for sensing lung fluid of a patient.

As used herein, the term lung fluid refers to pleural effusion and/orpulmonary edema. The term lung fluid may refer to one or more types oflung fluid, for example, exudate and/or transudate of various types andblood.

As used herein, the feeding tube may sometimes be interchanged with theterm nasogastric tube. For example, rather than a feeding tube (i.e.,for delivery of enteral feedings to the stomach and/or digestive system)a nasogastric tube (i.e., for removal of fluid from the stomach and/ordigestive system) may be used. It is noted that in some cases adedicated catheter may be used for monitoring for lung fluid.

An aspect of some embodiments of the present invention relates tosystems, methods, an apparatus, and/or code instructions (stored in adata storage device, executable by one or more hardware processor(s))for sensing lung fluid of a target patient. A feeding tube including atleast one intra-body electrode (which may also act as a sensor) at itsdistal end is located within the esophagus and/or stomach. Theintra-body electrode(s) is positioned in proximity to and/or in contactwith the lower esophagus sphincter (LES) of the target patient, aboveand/or below the LES, within the esophagus and/or stomach. One or morealternating currents (AC) at different frequencies are applied betweenthe intra-body electrode(s) and one or more extracorporeal electrode(s)applied to the surface of the skin of the target individual. Thealternating current(s) is transmitted between the intra-bodyelectrode(s) and the extracorporeal electrode(s) through the lung(s). Anestimated of the amount of lung fluid and/or the change of lung fluidrelative to a baseline measurement in one lung or each one of thepatient's lungs is computed according to a measurement(s) outputted bythe intra-body electrode(s) and/or the extracorporeal electrode(s).Optionally, the estimated of the amount of lung fluid is computedaccording to an impedance value(s) computed based on the applied ACcurrent and measured voltage.

As used herein, the phrase the estimated amount of lung fluid maysometime be interchanged with the phrase the estimated change of lungfluid relative to a baseline. The systems, methods, apparatus, and/orcode instructions described herein may estimate the absolute amount oflung fluid, and/or estimate the change of lung fluid relative to aninitial baseline measurement.

The systems, methods, apparatus, and/or code instructions describedherein relate to the technical problem of monitoring for accumulation oflung fluid. In particular, continuously (or near continuously, forexample, at closely spaced intervals, for example, every minute, 5minutes, or 10 minutes) monitoring the amount of lung fluid. Thetechnical problem may relate to monitoring for a clinically significantamount of lung fluid, and/or a prediction of a risk of developing aclinically significant amount of lung fluid. The clinically significantamount of lung fluid may affect the patient's breathing, and/or mayrequire treatment (e.g., drainage) and/or further investigation ofunderlying causes. Prediction of risk of impending accumulation ofclinically significant amount of lung fluid may trigger early treatmentto prevent the accumulation, for example, treatment of early heartfailure before the lung fluid accumulates.

The systems, methods, apparatus, and/or code instructions describedherein may relate to the technical problem of safety detecting lungfluid. In contrast, some other approaches are based on an electrodepositioned within or in proximity to the heart. When lung fluid ismeasured by these approaches, current is passed through the heart, whichincreases the risk of, for example, of an arrhythmia. In contrast, thesystems, methods, apparatus, and/or code instructions described hereinare based on locating sensor(s) away from the heart, optionally inproximity to the lower esophageal sphincter, which prevent passages ofelectrical current through the heart, or significantly reduce electricalcurrent through the heart to safe levels. Some other approaches arebased on electrodes located externally to the skin of the patient. Thecurrent applied between such electrodes may entirely bypass the lung, ormostly bypass the lung, resulting in inaccurate measurements that areunable to correctly sense the amount of lung fluid. In contrast, thesystems, methods, apparatus, and/or code instructions described hereinare based on sandwiching one or each lung between the electrodes, whichdirects most or all of the current.

Some implementations of the systems, methods, apparatus, and/or codeinstructions described herein improve the performance of existing tubesand/or electrodes, which are positioned with the esophagus of thepatient for other reasons, for example, a nasogastric tube for removingfluid from the stomach and/or digestive system of the patient, and/or anenteral feeding tube for delivering enteral feedings to the stomachand/or digestive system of the patient. The impedance readings obtainedby the electrodes, which may be obtained for other reasons (e.g.,determine a reflux event, monitor correct positioning of the tube,and/or estimate amount of fluid in the stomach) may be further utilizedto monitor the patient for accumulation of lung fluid. The patient maybe monitored for accumulation of lung fluid while the tube and/orelectrodes are utilized for other purposes. For example, while anintubated patient is being enterally fed over a 24 period, the feedingtube is simultaneously utilized for monitoring for accumulation of lungfluid.

The systems, methods, apparatus, and/or code instructions describedherein do not simply perform automation of a manual procedure, butperform additional automated features which cannot be performed manuallyby a human using pencil and/or paper. According to current practice,detection of lung fluid is generally a medical art, based on thephysical performing one or more of the following: observation ofbreathing difficulty, detection of low oxygen saturation, auscultationof the lungs, analysis of a chest x-ray, and performing an analysis ofpleural fluid (which is obtained by a painful procedure in which aneedle is inserted into the pleural space). Lung fluid is more reliablydetected based on images acquired by advanced imaging modalities, forexample, computed tomography (CT) and magnetic resonance imaging (MRI),which however are not always available, and take time to analyze.Monitoring the development of lung fluid according to current practiceis difficult, and unreliable. Moreover, current methods are based onestimating existing lung fluid, and do not relate to prediction of riskof accumulation of lung fluid. In contrast, the systems, methods,apparatus, and/or code instructions described herein provide real-time,optionally continuous, monitoring of the amount of lung fluid, real-timedetection of accumulation of a clinically significant amount of lungfluid, and/or optionally predict a risk of accumulation of an excessamount of lung fluid in the near future. An indication of the monitoringand/or prediction is generated, which provides healthcare workers withearly and/or advanced notification for taking preventing action and/orearly treatment to avoid complications and/or consequences of delayeddiagnosis and treatment.

When the features related to by the systems, methods, apparatus, and/orcode instructions described herein are taken as a whole, the combinationof the features amounts to significantly more than a simple mathematicalcalculation of computing impedance value(s) and estimating the amount oflung fluid according to the impedance value(s). The systems, methods,apparatus, and/or code instructions described herein do not merelyrelate to mathematical computations (e.g., equations), but relate to theparticular data collected, stored, and the way the data is collected byelectrodes, and optionally performing a prediction of likelihood of animpending accumulation of a clinically significant amount of lung fluid.

The systems, methods, apparatus, and/or code instructions describedherein improve an underlying technical process within the technicalfield of automated patient monitoring, in particular, within the fieldof automated monitoring of lung fluid.

The systems, methods, apparatus, and/or code instructions describedherein provide a unique, particular, and advanced technique ofmonitoring lung fluid, and optionally predicting likelihood of animpending accumulation of a clinically significant amount of lung fluid.

The systems, methods, apparatus, and/or code instructions describedherein are tied to physical real-life components, for example, one ormore of: electrode(s) that measure impedance, a feeding tube (e.g.,nasogastric tube, enteral feeding tube) on which one or more electrodesare disposed, computational hardware (e.g., hardware processor(s),physical memory device) that analyzes the electrode output, and adisplay that presents the estimated amount of lung fluid and/or presentsthe indication of prediction of likelihood of an impending accumulationof a clinically significant amount of lung fluid.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings and/or the Examples. The invention iscapable of other embodiments or of being practiced or carried out invarious ways.

The present invention may be a system, a method, and/or a computerprogram product. The computer program product may include a computerreadable storage medium (or media) having computer readable programinstructions thereon for causing a processor to carry out aspects of thepresent invention.

The computer readable storage medium can be a tangible device that canretain and store instructions for use by an instruction executiondevice. The computer readable storage medium may be, for example, but isnot limited to, an electronic storage device, a magnetic storage device,an optical storage device, an electromagnetic storage device, asemiconductor storage device, or any suitable combination of theforegoing. A non-exhaustive list of more specific examples of thecomputer readable storage medium includes the following: a portablecomputer diskette, a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory (EPROMor Flash memory), a static random access memory (SRAM), a portablecompact disc read-only memory (CD-ROM), a digital versatile disk (DVD),a memory stick, a floppy disk, and any suitable combination of theforegoing. A computer readable storage medium, as used herein, is not tobe construed as being transitory signals per se, such as radio waves orother freely propagating electromagnetic waves, electromagnetic wavespropagating through a waveguide or other transmission media (e.g., lightpulses passing through a fiber-optic cable), or electrical signalstransmitted through a wire.

Computer readable program instructions described herein can bedownloaded to respective computing/processing devices from a computerreadable storage medium or to an external computer or external storagedevice via a network, for example, the Internet, a local area network, awide area network and/or a wireless network. The network may comprisecopper transmission cables, optical transmission fibers, wirelesstransmission, routers, firewalls, switches, gateway computers and/oredge servers. A network adapter card or network interface in eachcomputing/processing device receives computer readable programinstructions from the network and forwards the computer readable programinstructions for storage in a computer readable storage medium withinthe respective computing/processing device.

Computer readable program instructions for carrying out operations ofthe present invention may be assembler instructions,instruction-set-architecture (ISA) instructions, machine instructions,machine dependent instructions, microcode, firmware instructions,state-setting data, or either source code or object code written in anycombination of one or more programming languages, including an objectoriented programming language such as Smalltalk, C++ or the like, andconventional procedural programming languages, such as the “C”programming language or similar programming languages. The computerreadable program instructions may execute entirely on the user'scomputer, partly on the user's computer, as a stand-alone softwarepackage, partly on the user's computer and partly on a remote computeror entirely on the remote computer or server. In the latter scenario,the remote computer may be connected to the user's computer through anytype of network, including a local area network (LAN) or a wide areanetwork (WAN), or the connection may be made to an external computer(for example, through the Internet using an Internet Service Provider).In some embodiments, electronic circuitry including, for example,programmable logic circuitry, field-programmable gate arrays (FPGA), orprogrammable logic arrays (PLA) may execute the computer readableprogram instructions by utilizing state information of the computerreadable program instructions to personalize the electronic circuitry,in order to perform aspects of the present invention.

Aspects of the present invention are described herein with reference toflowchart illustrations and/or block diagrams of methods, apparatus(systems), and computer program products according to embodiments of theinvention. It will be understood that each block of the flowchartillustrations and/or block diagrams, and combinations of blocks in theflowchart illustrations and/or block diagrams, can be implemented bycomputer readable program instructions.

These computer readable program instructions may be provided to aprocessor of a general purpose computer, special purpose computer, orother programmable data processing apparatus to produce a machine, suchthat the instructions, which execute via the processor of the computeror other programmable data processing apparatus, create means forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks. These computer readable program instructionsmay also be stored in a computer readable storage medium that can directa computer, a programmable data processing apparatus, and/or otherdevices to function in a particular manner, such that the computerreadable storage medium having instructions stored therein comprises anarticle of manufacture including instructions which implement aspects ofthe function/act specified in the flowchart and/or block diagram blockor blocks.

The computer readable program instructions may also be loaded onto acomputer, other programmable data processing apparatus, or other deviceto cause a series of operational steps to be performed on the computer,other programmable apparatus or other device to produce a computerimplemented process, such that the instructions which execute on thecomputer, other programmable apparatus, or other device implement thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

The flowchart and block diagrams in the Figures illustrate thearchitecture, functionality, and operation of possible implementationsof systems, methods, and computer program products according to variousembodiments of the present invention.

In this regard, each block in the flowchart or block diagrams mayrepresent a module, segment, or portion of instructions, which comprisesone or more executable instructions for implementing the specifiedlogical function(s). In some alternative implementations, the functionsnoted in the block may occur out of the order noted in the figures. Forexample, two blocks shown in succession may, in fact, be executedsubstantially concurrently, or the blocks may sometimes be executed inthe reverse order, depending upon the functionality involved. It willalso be noted that each block of the block diagrams and/or flowchartillustration, and combinations of blocks in the block diagrams and/orflowchart illustration, can be implemented by special purposehardware-based systems that perform the specified functions or acts orcarry out combinations of special purpose hardware and computerinstructions.

As used herein, the term clinically significant lung fluid, or lungfluid, refers to an amount of fluid in the lungs that poses a healthrisk to the patient (e.g., in terms of difficulty breathing, and/orreduced oxygen saturation), and/or requires treatment. It is noted thatsome excess lung fluid may be tolerated. The amount of fluid that isconsidered as clinically significant may vary, for example, by patientand/or by treating physician, and/or according to the type of fluid(e.g., source, transudate, exudates, mostly water, blood, pus). Thethreshold separating between clinically significant and non-clinicallysignificant lung fluid may be set, for example, manually by a user(e.g., via a graphical user interface), obtained from a stored systemparameter, and/or automatically computed by code (e.g., based on ananalysis of the patient health record.

As used herein, the terms electrode and sensor are sometimesinterchangeable. Reference is now made to FIG. 1 , which is a flowchartof a method for sensing lung fluid of a target patient based on at leastone electrode positioned within the esophagus and/or stomach of a targetpatient, in accordance with some embodiments of the present invention.Reference is also made to FIG. 2 , which is a schematic of components ofa system 200 for sensing lung fluid of a target patient based on atleast one intra-body electrode 202 positioned within the esophagusand/or stomach of a target patient, in accordance with some embodimentsof the present invention. One or more of the acts of the methoddescribed with reference to FIG. 1 may be implemented by components ofsystem 200, as described herein, for example, by a processor(s) 204 of acomputing device 206 executing code instructions 208A stored in a memory208 (also referred to herein as a data storage device).

Computing device 206 receives electrical signals outputted by intra-bodyelectrode(s) 202 and/or extracorporeal electrode(s) 210. Intra-bodyelectrode(s) 202 are positioned on a feeding tube 212. At least oneintra-body electrode 202 is located on the distal end of feeding tube212, such that when feeding tube 212 is inserted into the esophagus ofthe target patient, intra-body electrode 202 is positioned in proximityto the lower esophageal sphincter (LES), for example, above the LESwithin the esophagus, or within the stomach (e.g., the antrum of thestomach).

Intra-body electrode(s) 202 may be associated with an expandable element214 located on the distal end of feeding tube 212, for example, aninflatable balloon, an expanding mesh made out of memory metal, and/or asponge. Expandable element 214 is expanded (e.g., inflated,self-expanding) when feeding tube 212 is positioned within theesophagus, creating a contact (optionally by applying a force) betweenintra-body electrode(s) 202 and the inner wall of the esophagus and/orstomach. The contact transmits electrical signals and/or current betweenintra-body electrode(s) 202 and the nearby tissue.

Optionally feeding tube 212 is implemented as an enteral feeding tubefor feeding the patient. The enteral feeding tube is positioned withinthe gastrointestinal system of the patient, for example, within thestomach, duodenum, or upper small intestine. Patients being enterallyfed may be monitored for accumulation of clinically significant lungfluid without requiring insertion of an additional probe, since theenteral feeding tube is already necessary to feed the patient.Intra-body electrode(s) 202 is positioned in proximity to the LES whenthe enteral feeding tube is in the proper feeding position. The enteralfeeding tube provides an additional function of monitoring the patientfor accumulation of clinically significant lung fluid.

Alternatively or additionally, feeding tube 212 is implemented as anasogastric (NG) tube for evacuation of contents from the stomach. TheNG tube is positioned within the gastrointestinal system of the patient,for example, within the stomach, duodenum, or upper small intestine.Patients having their stomach contents being drained and/or stomachmaintained in a drained state may be monitored for accumulation ofclinically significant lung fluid without requiring insertion of anadditional probe, since the NG tube is already necessary to treat thepatient. Intra-body electrode(s) 202 is positioned in proximity to theLES when the NG tube is in the proper stomach content draining position.The NG tube provides an additional function of monitoring the patientfor accumulation of clinically significant lung fluid.

Intra-body electrode(s) 202 may be associated with an attachmentmechanism, optionally a clip-on attachment, for example, a clip, aC-shaped clip, for connection to existing off-the-shelf feeding tubes212. Alternatively, enteral feeding tubes are manufactured integrallywith intra-body electrode(s) 202, for example, intra-body electrode(s)202 are glue, crimped, injection molded, and/or build-in to the outersurface of the enteral feeding tube.

Alternatively, feeding tube 212 is implemented as an elongated catheter.The catheter may include one or more lumens that house wires fortransmission of signals between intra-body electrode(s) 202 andcomputing device 206.

Extracorporeal electrode 210 may be implemented as a pad electrode.Extracorporeal electrode 210 is designed for placement externally to theskin of the target patient. Extracorporeal electrode 210 may include asticky portion for sticking to the surface of the skin. Extracorporealelectrode 210 may be positioned over the surface of the skin, with anoptional conduction medium (e.g., gel) providing electrical conductivitybetween extracorporeal electrode 210 and the skin.

Electrodes 202 and/or 210 may include one or more electrodes that applya currently and/or measure an applied current. Optionally, an electrodecomponent of electrode(s) 202 and/or 210 applies the current and aelectrode component of electrode(s) 202 and/or 210 senses the appliedcurrent. Alternatively or additionally, a single electrode may performthe functions of applying the current and sensing the current.Optionally, the extracorporeal (i.e., skin) electrodes may be mounted onboth sides of the skin of the patient and/or around the thorax, enablingthe independent measurement of lung fluid for each lung.

Computing device 206 may receive the outputs of electrodes 202 and/or210 via one or more electrode interfaces 216, for example, a networkinterface, a wire connection, a wireless connection, a local bus, otherphysical interface implementations, and/or virtual interfaces (e.g.,software interface, application programming interface (API), softwaredevelopment kit (SDK)).

Electrodes 202 and/or 210 may connect wirelessly and/or via wires withelectrode interface 216 of computing device 206.

Computing device 206 may be implemented as, for example, a standaloneintegral unit, a virtual machine, a client terminal, a server, acomputing cloud, a mobile device, a desktop computer, a thin client, aSmartphone, a Tablet computer, a laptop computer, a wearable computer,glasses computer, and a watch computer. Computing device 206 may beimplemented as a customized unit that include locally stored softwareand/or hardware that perform one or more of the acts described withreference to FIG. 1 . Alternatively or additionally, computing device206 may be implemented as code instructions loaded on an existingcomputing device. Alternatively or additionally, computing device 206may be implemented as hardware and/or code instructions (e.g., anaccelerator card) installed and/or integrated within an existingcomputing device.

Processor(s) 204 of computing device 206 may be implemented, forexample, as a central processing unit(s) (CPU), a graphics processingunit(s) (GPU), field programmable gate array(s) (FPGA), digital signalprocessor(s) (DSP), and application specific integrated circuit(s)(ASIC). Processor(s) 204 may include one or more processors (homogenousor heterogeneous), which may be arranged for parallel processing, asclusters and/or as one or more multi core processing units.

Memory 208 stores code instructions executable by processor(s) 204.Memory 208 is implemented as, for example, a random access memory (RAM),virtual memory, read-only memory (ROM), and/or a storage device, forexample, non-volatile memory, magnetic media, semiconductor memorydevices, hard drive, removable storage, and optical media (e.g., DVD,CD-ROM). Memory 208 stores code instructions 208A that implement one ormore acts of the method described with reference to FIG. 1 .Alternatively or additionally, one or more acts of the method describedwith reference to FIG. 1 are implemented in hardware.

As used herein, the term code instructions may refer to a softwareimplementation in which one or more hardware processors execute codestored in a memory, and/or a hardware implementation. For example,computing device 206 may include a circuit designed for impedanceestimation, for example, AFE4300 available from Texas Instruments.

Computing device 206 may include a data storage device 218 for storingdata, for example, a history of computed impedance values and/orestimated amounts of lung fluid. Data storage device 218 may beimplemented as, for example, a memory, a local hard-drive, a removablestorage unit, an optical disk, a virtual memory, a storage device,and/or as a remote server and/or computing cloud (e.g., accessed via anetwork connection).

Computing device 206 includes and/or is in communication with a userinterface 220 that includes a mechanism for a user to enter data (e.g.,patient information) and/or view presented data (e.g., estimated amountof lung fluid, trend of amount of lung fluid). Exemplary user interfaces220 include, for example, one or more of, a touchscreen, a display, akeyboard, a mouse, and voice activated software using speakers andmicrophone. External devices, such as client terminals 222 and/orserver(s) communicating with computing device 206 over a network mayserve as user interface 220, for example, a smartphone running anapplication may establish communication (e.g., cellular, network, shortrange wireless) with computing device 206 over network 226 using acommunication interface (e.g., network interface, cellular interface,short range wireless network interface). The user may enter data and/orview data on the display of the smartphone, optionally via a graphicaluser interface (GUI) application.

Computing device 206 may be in communication with client terminal(s) 222and/or server(s) 224 over network 226 via a network interface 228.Network interface 228 may be implemented as, for example, a networkinterface card, a hardware interface card, a wireless interface, aphysical interface for connecting to a cable, a virtual interfaceimplemented in software, communication software providing higher layersof connectivity, and/or other implementations.

Client terminal(s) 222 and/or server(s) 224 may receive indicationsgenerated by computing device 206, for example, currently computedestimate of amount of lung fluid, computed trend of amount of lungfluid, warning that amount of lung fluid is clinically significant,and/or a prediction warning that the trend of the amount of lung fluidis indicating of an impending accumulation of a clinically significantamount of lung fluid. Exemplary client terminal(s) 222 include: a mobiledevice, a smartphone, a tablet computer, a remotely located personalcomputer, a glasses computer, and a watch computer. Exemplary server(s)224 include: a hospital medical record server (e.g., the transmitteddata may be automatically logged into the patient electronic medicalrecord), and/or a remote monitoring station (e.g., nurses station thatmonitors multiple patients on the ward).

Referring now back to act 102 of FIG. 1 , the intra-body electrode(s)202 are positioned within the esophagus of the patient, and/or withinthe stomach of the patient. Intra-body electrode(s) 202 are positionedby placement of feeding tube 212 within the esophagus and/or stomach ofthe patient.

Intra-body electrode(s) 202 may be first connected to an off-the-shelffeeding tube, for example, by a C-shaped clamp connector of intra-bodyelectrode(s) 202 designed to snap tightly to a distal end of feedingtube 212. Alternatively, intra-body electrode(s) 202 are pre-connectedto feeding tube 212.

Optionally, intra-body electrode(s) 202 located a defined location(s)along the distal end portion of feeding tube 212 and are positionedcorrectly within the patient when feeding tube 212 is positioned withinesophagus and/or stomach according to the intended purpose of feedingtube 212. For example, when feeding tube 212 is implemented as anasogastric (NG) tube for evacuation of stomach contents, intra-bodyelectrode(s) 202 located at the distal end of the NG tube are correctlypositioned when NG tube is correctly positioned for the evacuation ofstomach contents. In another example, when feeding tube 212 isimplemented as a enteral feeding tube (inserted into the patient via thenose, the mouth, and/or a surgically created orifice) for enteralfeeding of the patient, intra-body electrode(s) 202 located at thedistal end of the feeding tube are correctly positioned when the feedingtube is correctly positioned for feeding of the patient. When feedingtube 212 is designed as a catheter, the catheter may be designed tocorrectly position intra-body electrode(s) 202 within the esophagus, forexample, by a defined length of the catheter, and/or a shape of thecatheter designed to stop at the LES.

Feeding tube 212 may include multiple intra-body electrodes 212 spacedapart from one another, and located along the length of feeding tube212. The multiple intra-body electrodes 212 may generate a tomographicalimpedance map of fluid in the lung according to their respectivelocations.

At least one of intra-body electrodes 202 is located in proximity to theLES, for example, contacting the LES, or less than about 1 centimeter(cm), or 3 cm, or 5 cm, or 10 cm, or other values. The intra-bodyelectrode 202 may be located above the LES (within the esophagus), orbelow the LES (e.g., within the stomach, optionally the antrum).

The location of intra-body electrodes 202 in proximity to the LESpositions intra-body electrodes 202 below the level of the heart, and/orin proximity to the base of the lung(s) where fluid begins toaccumulate. The impedance measurement obtained by the intra-bodyelectrodes 202 in proximity to the LES avoids or reduces current throughthe heart. Alternatively or additionally, the impedance measurementobtained by the intra-body electrodes 202 in proximity to the LES isindicative of fluid at the base of the lung(s), where the fluid maybegin to accumulate, to obtain an early indication of clinicallysignificant accumulation of lung fluid.

Intra-body electrode(s) 202 are placed in contact with the inner wall ofthe esophagus and/or stomach. Optionally, expandable element 214 appliesa force to contact intra-body electrode(s) 202 with the inner wall ofthe esophagus and/or stomach, for example, by expanding a balloon,and/or self-expansion of memory metal.

Intra-body electrode(s) 202 may be positioned below the axial plane ofthe heart.

At 104, extracorporeal electrode(s) 210 are positioned. Extracorporealelectrode(s) 210 may be stuck to the skin of the patient, for example,by a sticky pad and/or tape. A conductive gel may be applied to improveelectrical coupling between extracorporeal electrode(s) 210 and the skinof the target patient.

Exemplary locations for positioning of extracorporeal electrode(s) 210include: along the lower rib or slightly above the lower rib (e.g.,within about 5-10 centimeter), at the axillary line (e.g., anterior,mid, posterior), mid clavicular line, and one the back in proximity tothe spine and/or between the spine and posterior axillary line.

Extracorporeal electrode(s) 210 may be positioned below the axial planeof the heart.

The location of extracorporeal electrode(s) 210 may impact the type oflung fluid that is being monitored. Optionally, one or moreextracorporeal electrode(s) are positioned on the skin of the patientcorresponding to one or more lobes of the lungs, optionally the base ofthe lungs. The lobe(s) of the lung(s) may be monitored for pulmonaryedema, which accumulates within the alveoli of the lung itself, and mayaccumulate per lobe. For example, the extracorporeal electrode(s) may beplaced on the chest for monitoring the anterior lobe(s) and/or the rightmiddle lube, and/or placed on the back for monitoring the posteriorlobe(s). Alternatively or additionally, one or more extracorporealelectrode(s) are positioned on the skin of the patient corresponding tothe base of the lung, for example, for monitoring for pulmonary effusionwhich develops within the pleural space and tends to sink to the lowerpart o the pleural space around the base of the lung.

Pulmonary edema may be differentiated from pleural effusion according tothe impedance values measured by multiple extracorporeal electrode(s) atdifferent locations. For example, impedance values that are relativelylower at specific electrodes at positions corresponding to specificlobes may be indicative of pulmonary edema, whereas impedance valuesthat are relatively lower at the base of the lung but relativelyconstant elsewhere may be indicative of pulmonary effusion.

Extracorporeal electrode(s) 210 may be positioned on the skin of thepatient at a location corresponding to the costophrenic angle (e.g., formonitoring for pulmonary effusion).Extracorporeal electrode(s) 210 maybe positioned as far away from the heart as possible, but at the sametime at a location(s) corresponding to the lung(s).

Extracorporeal electrodes 210 may be positioned for parallel monitoringof both left and right lungs for accumulation of clinically significantamount of fluid.

As discussed herein, the locations of intra-body electrode(s) 202 inproximity to the LES and the location of extracorporeal electrode(s) 210prevent applied AC from reaching the heart, and/or reduce the portion ofthe AC that reaches the heart to safe levels. Electrodes may be mountedon the skin around the torso. The exact location and/or number ofelectrodes may be determined, for example, by the physician depending onthe patient's condition.

Reference is now made to FIG. 3 , which is a schematic depicting adangerous set-up of measuring lung fluid based on other proposedapproaches, to illustrate the safe set-up according to some embodimentsof the present invention. Other proposed approaches are based ongenerating a current 302 that passes through a heart 304 of the targetpatient for sensing fluid within a lung 306 of the patient. Current 302passing through heart 304 greatly increases the risk of arrhythmias, andmay damage and/or interfere with devices implanted within heart 304, forexample, a pacemaker. Current 302 passes between one electrodepositioned within heart 304 and another electrode positioned inproximity to lung 306, resulting in current 302 travelling through bothlung 306 and heart 304 to generate output 308 Output 308 is analyzed tosense fluid within lung 306. It is noted that the analysis of output 308includes additional irrelevant data of heart 304, and therefore is lessaccurate in sensing fluid within lung 306.

Reference is now made to FIG. 4 , which is a schematic depicting a safeset-up of measuring lung fluid in lung 306 based on current 402 passingthrough lung 306 while avoiding passing through heart 304, in accordancewith some embodiments of the present invention. The set-up describedwith reference to FIG. 4 , based on embodiments described herein, is incontrast to the set-up according to other approach as described withreference to FIG. 3 . It is noted that some current may pass throughheart 304, however such current is weak and unable to triggerarrhythmias and/or interfere with devices implanted in heart 304.Current 402 passes through lung 306 while avoiding heart 304 based onthe positioning of intrabody electrode(s) at the distal end portion ofesophagus 410 (e.g., in proximity to the LES) and/or at the entrance ofstomach 412 (e.g., within the antrum), and the positioning ofextracorporeal electrode(s) on the surface of the patient's skin inproximity to lung 306. The fluid in lung 306 is sensed based on ananalysis of output 408 indicative of the impedance of the current 402passing through lung 306.

At 106, one or more alternating current (AC) are applied. AC currentsmay be applied at different frequencies, to compute a set of impedancevalues measured at each respective different frequency. For example, adefined pattern of AC frequencies may be applied sequentially, forexample, a single frequency during a single time interval.

The accumulated results may be presented to the physician, optionallybased on a Cole—Cole type diagram.

The following are some examples of set-ups for applying the AC currentand 10 performing a measurement, optionally of voltage:

When the AC current is applied between intra-body electrode 202 and theextra corporal electrode 210. Voltage is measured by between intra-bodyelectrode 202 and extracorporeal electrode 210 of one or both lungs.Voltage of both lungs may be measured simultaneously. In implementationof multiple intra-body electrodes 202 and/or multiple extracorporealelectrodes 210, different activation patterns of a single intra-bodyelectrode 202 and/or a single extracorporeal electrode 210 may beapplied.

At 108, output is received from extracorporeal electrode(s) 210 and/orintra-body electrode(s) 202. Optionally, the output includes anindication of a measured voltage (e.g., voltage drop) betweenextracorporeal electrode(s) 210 and intra-body electrode(s) 202. It isnoted that extracorporeal electrode(s) 210 and/or intra-bodyelectrode(s) 202 may act as sensors. Alternatively, the sensing featureis performed by a sensor component of extracorporeal electrode(s) 210and/or intra-body electrode(s) 202.

Optionally, the output is sensed while the alternating current isapplied.

At 110, impedance is computed. Optionally, the impedance is computed foreach lung, or for one lung. The impedance may be computed according tothe applied alternating current and the measured voltage.

In terms of mathematical representation, the applied alternating currentis denoted as I₀e^(ωt)

where I₀ denotes the amplitude of the current and ω denotes thefrequency.

The equivalent impedance across the tissues, including the lung and anyfluid therein, between intra-body electrode 202 and extracorporealelectrode 210 may be mathematically represented based on the followingrelationship:

Z_(L) =  = V₀e^(i(ωt − θ))/I₀e^(iωt)

Where d V₀e^(i(ωt-θ)) measured between intrabody electrode 202 andextracorporeal electrode 210.

The current may be applied by an AC microampere source 610.

The voltage may be measured by an instrumentation amplifier 612.

The impedance may be computed according to the measured voltage andapplied current based on the above described relationship by computingdevice 206 (e.g., by hardware processor(s) 204) executing code 208Astored in memory 208). The estimated amount of fluid and/or the computedimpedance may be presented within a GUI (e.g., as a real-time value, asa graph indicative of a trend over a recent time interval) on a display220.

Reference is now made to FIG. 5 , which is a schematic depicting anexemplary positioning of intra-body electrode 202 and extracorporealelectrode(s) 210 for sensing fluid 502 in one or more lungs 504 of atarget individual, in accordance with some embodiments of the presentinvention.

Intra-body electrode 202 may be positioned within the esophagus, abovethe LES, and/or approximately corresponding to the location of thediaphragm. One or more extracorporeal electrode(s) 210 are associatedwith each lung 504. Extracorporeal electrode(s) 210 are positioned onthe skin of the patient in proximity to the lung 504 lying beneath theskin. Extracorporeal electrode(s) 210 may be positioned in proximity tothe base of each lung 504, since fluid 502 accumulates starting from thebase of each lung 504.

Schematic 510 depicts the state of lung(s) 504 of the patient withoutany (or clinically insignificant amount of) excess fluid. Impedancevalues measured between intra-body electrode 202 and extracorporealelectrode(s) 210 are relatively high 512.

Schematic 514 depicts the state of lung(s) 504 of the patient with aclinically significant amount of excess fluid 502. Impedance valuesmeasured between intra-body electrode 202 and extracorporealelectrode(s) 210 are relatively low 516.

Reference is now made to FIG. 6 , which is a schematic depicting anelectrical setup for measurement of impedance across a lung of targetindividual for sensing fluid within the lung, in accordance with someembodiments of the present invention. Lung impedance is denoted as 604.An alternating current (AC) is applied to the lung via intra-bodyelectrode(s) 202 and sensed by extracorporeal electrode(s) 210.Intrabody electrode 202 is located at a height corresponding to adiaphragm 606 and/or above the LES. Alternatively or additionally, ACcurrent is applied by extracorporeal electrode(s) 210 and sensed byintra-body electrode(s) 202. Alternatively or additionally, AC currentis applied by both extracorporeal electrode(s) 210 and intra-bodyelectrode(s) 202 and sensed by both extracorporeal electrode(s) 210 andsensed by intra-body electrode(s) 202, for example, applied by anelectrode component of extracorporeal electrode 210 and sensed by asensor component of extracorporeal electrode 210.

Reference is now made to FIG. 7 , which is a schematic depicting anabstract representation of the electrical setup for measurement ofimpedance across a lung of target individual for sensing fluid withinthe lung, in accordance with some embodiments of the present invention.A low current AC source 710 applies the AC to a lung tissue 720 andother nearby tissues that include auxiliary resistance 722. Aninstrumentation amplifier 712 measures the voltage across lung tissue720, between the intra-body electrode(s) and the extracorporealelectrode(s). A processor(s) and/or controller 706 (e.g., computingdevice 206 described with reference to FIG. 2 ) computes the impedanceacross lung tissue 720 based on the AC applied by source 710 and thevoltage measured by instrumentation amplifier 712. The computedimpedance and/or estimate of the corresponding amount of lung fluid isprovided to a hub and/or or presentation on monitor (e.g., within a GUI)720.

Reference is now made to FIG. 8 , which is a schematic of an environmentset-up for sensing fluid within a lung(s) 820 of a target patient basedon an intra-body electrode(s) 802 positioned along a feeding tube 812located within an esophagus 826 of a target individual, in accordancewith some embodiments of the present invention. At least one intra-bodyelectrode 802 is located on feeding tube 812 at a location correspondingto the LES when feeding tube 812 is correctly positioned withinesophagus 826 and a stomach 822 of the target individual. Additionalelectrodes 824 may be positioned along the length of feeding tube 812,above and/or below the location of intra-body electrode 802 located atthe position corresponding to the LES. A console 828 (e.g., computingdevice) receives controls application of an alternative current tointra-body electrodes 802 and optionally other electrodes 824 located onfeeding tube 812. Console 828 receives voltage measurements sensed byextracorporeal electrodes 810. Alternatively or additionally, console828 applies AC via extra-corporeal electrodes 810 and receives voltagemeasurements performed by intra-body electrodes 802 and optionallyelectrodes 824. Console 828 computes the impedance across lung(s) 820according to the applied AC and measured voltage(s). An indication ofclinically significant or clinically insignificant or no fluid inlung(s) 820 may be generated accordingly, and optionally presented on adisplay within a GUI, for example, as a trend line.

Reference is now made to FIG. 9 , which is a schematic of an electronicmeasurement system for sensing fluid within one or more lungs of apatient based on at least one intra-body electrode positioned within theesophagus in proximity to the LES, in accordance with some embodimentsof the present invention. Component 902 represents a model of thetissues between the intra-body electrode positioned within the esophagusin proximity to the LES, and an extracorporeal electrode. The tissuesmostly include the lung, and other associated tissues, for example, boneand muscle. The tissues are modeled as including one or more capacitorsand one or more resistors. Component 904 represents circuitry thatgenerates AC currents and receives measurements of voltage from theelectrodes, as described with reference to FIG. 6 and/or 7 .Processor(s) 906 computes the impedance according to the generated ACand measured voltage, as described herein. An indication of theimpedance and/or sensed amount of lung fluid is provided for display908, for example, within a GUI on a display.

At 112, an indication of an estimated amount of lung fluid (e.g.,absolute amount, and/or change relative to a baseline) in one or bothlungs of the patient is computed. The indication is computed based onthe measured impedance values. Optionally, the computed impedancevalue(s) is mapped to the estimated amount of lung fluid.

The amount of lung fluid change may be independently estimated for eachlung, according to impedance values computed based on the extracorporealelectrodes applied to the skin corresponding to teach lung.

The amount of lung fluid change may be estimated according to an initialbaseline measurement performed at the start of the monitoring process.

The amount of lung fluid change may be estimated as a relativecomparison between impedance values measured for the two lungs. Thechange in the lung fluid for each lung may be compared, for example, theimpedance change of the left lung relative to baseline as a ratio of theimpedance change of the right lung relative to baseline. The comparisonbetween the two lungs may be help to differentiate between lung fluidprocesses that affect both lungs equally from lung fluid processes thataffect only one lobe or only one lung (or affect one lobe or lung morethan the others).

The computed impedance value may be mapped to a classification categoryof clinically significant amount of lung fluid, or clinicallyinsignificant amount of lung fluid (which may include the absence oflung fluid). Alternatively or additionally, the computed impedance valueis mapped to a relative amount of lung fluid relative to a thresholdthat separates between clinically significant and clinicallyinsignificant amount of lung fluid, for example, indicative of severity.Alternatively or additionally, the computed impedance value is mapped toan estimated amount of lung fluid.

The computed impedance value may be mapped to an impedance score. Theimpedance score is relative to the threshold differentiating betweenclinically significant and clinically insignificant amount of lungfluid. The impedance score includes a value and an associated time stampindicative of the time at which the impedance value is measured. Theimpedance score may be presented on a graph of impedance scores obtainedover time, as described herein.

The mapping between the impedance value and the estimated amount of lungfluid may be performed based on empirical data collected from sampledindividuals, for example, measurements of impedance values performed onsample individuals for which a manual indication of the amount of lungfluid is estimated (e.g., an absolute amount of lung fluid which may bemeasured for example based on a thoracentesis in which the lung fluid iswithdrawn into a calibrated container and the volume of the lung fluidis measured, and/or indication of clinically significant or clinicallyinsignificant fluid determined based on clinical signs and/or symptoms).Alternatively or additionally, the mapping may be performed based on amathematical model of dielectric properties of the tissues.

The mapping between the impedance value and the estimated amount of lungfluid may be performed, for example, based on a dataset of theempirically collected values (e.g., graph, look-up able), and/or astatistical classifier trained based on the data (e.g., neural network,linear regression, support vector machine).

One or more impedance values may be mapped to a single indication of theestimated amount of lung fluid. For example, multiple impedance valuesmeasured according to different frequencies of alternating currents maybe aggregated and mapped to the single indication of estimated amount oflung fluid. The aggregation may include, for example, an average, and/ora weighted average computation of the impedance values.

Reference is now made to FIG. 10 , which is an exemplary graph 1002 foranalyzing the computed impedance value(s) for determining an indicationof a clinically significant amount of excess fluid in the lungs, inaccordance with some embodiments of the present invention. Graph 1002may be constructed based on, for example, impedance measurementsobtained from one or more sample patients with varying degrees of lungfluid and associated medical evaluation of a reference amount of lungfluid. In another example, graph 1002 may be constructed based on amathematical model, for example, computed according to the Cole-Coleequation as described with reference to Cole, Kenneth S, Robert H(1941). “Dispersion and Absorption in Dielectrics: I - AlternatingCurrent Characteristics”. Journal of

Chemical Physics. 9: 341-351. In yet another example, parameters of themathematical model are determined according to empirical data (impedancemeasurements on real patients).

It is noted that different graphs 1002 may be constructed foridentification of different types of lung fluid, for example,transudative (i.e., mostly water), and different types of exudative(e.g., blood, pus, infectious materials, water with high percentage ofother components). The type of lung fluid may be manually entered by auser (e.g., selected from a list presented on the GUI by clicking),and/or automatically determined by code instructions based on a sensor(e.g., based on an automated analysis of the lung fluid) and/or obtainedfrom an electronic medical record (e.g., based on a laboratory result).Alternatively, a common graph 1002 is constructed based on theassumption that the differences between the types of lung fluid are notstatistically significant in terms of detection of clinicallysignificant amounts.

Graph 1002 plots complex impedance values as a point within a complexplane defined relative to a real component axis (x-axis) 1004 and animaginary component axis (y-axis) 1006. Each impedance value may bemathematically represented as:

Z_(L)(ω)=R_(L)(ω)+iX_(L)(ω)

Where Z_(L)(ω) denotes the impedance value,

R_(L)(ω) denotes the real component,

X_(L)(ω) denotes the imaginary component, and

ω denotes the frequency of the applied alternating current.

It is noted that the frequency along the real component axis 1004increases from right to left, as represented by arrow 1008.

The impedance value measured or the target patient is plotted on graph1002, and analyzed as follows:

Impedance values plotted on graph 1002 that fall above a normalthreshold (denoted by curve 1010) denote a lung without fluid, and/orwith a normal amount of fluid, and/or with a clinically insignificantamount of fluid.

Impedance values plotted on graph 1002 that fall below a clinicallysignificant amount of lung fluid threshold (denoted by curve 1012)denote a lung with a clinically significant amount of fluid.

Impedance values plotted on graph 1002 that fall within intermediatezone 1014 (bordered by curves 1010 and 1012) denote a lung that is atimpending risk of accumulating a clinically significant amount of fluid.

Optionally, the lung impedance measurement and/or monitoring asdescribed herein is based on an initial baseline measurement, followedby continuous and/or periodic updating with reference to the baselinemeasurement, for example, the baseline impedance is calibrated to zero,and additional measurements are calibrated with reference to thebaseline value. The initial baseline impedance value and subsequenceimpedance values that are adjusted relative to the baseline may avoidthe natural physiological variance distribution amongst the population.

When the impedance values fall within zone 1014, alerts may be generated(e.g., presented within a GUI on a display) indicating that the patientis at impending risk of accumulating a clinically significant amount offluid. Indications of impedance values above threshold 1010 may begenerated and presented within the GUI for monitoring the patient.Alerts of impedance values below threshold 1012 may be generated andpresented within the GUI indicating that the patient has alreadyaccumulated a clinically significant amount of fluid.

Referring now back to FIG. 1 , at 114, a trend line is computedaccording to the impedance values and/or impedance scores.

When the impedance values are represented as complex values, the complexvalues may be converted into an impedance score representation suitablefor presentation, optionally as a point on a graph of impedance scores(e.g., along the y-axis) over time (e.g., along the x-axis). Theimpedance score representation may be computed as one of more of: thereal component of the complex impedance value, a real representation ofthe imaginary component of the complex impedance value, and a realrepresentation of the complex impedance value for example the length ofa vector representation of the complex impedance value (e.g., squareroot of the squared real component and the squared imaginary component).

Each impedance score is associated with the time at which the respectiveimpedance score is measured and/or computed.

The trend line is computed for the most recent impedance scores, forexample, the most recent predefined number of impedance scores, over arecent predefined time interval, and/or according to a set of rules thatdefined events for computation of the trend line.

The trend line may be computed, for example, as a regression line fittedto the recent impedance score over a recent time interval according to aleast square fit.

The trend line may be extended into the future for prediction likelihoodof impending accumulation of clinically significant lung fluid. Thelikelihood of impending accumulation of clinically significant lungfluid may be predicted when the trend line crosses within a futurepredefined interval of time, a threshold differentiating betweenclinically significant amount of fluid and clinically insignificantamount of fluid.

The probability of the likelihood of impending accumulation ofclinically significant amount of lung fluid may be computed, forexample, as a number and/or a classification category (e.g., high risk,intermediate risk, low risk). The probably may be computed according toa correlation value indicative of fit of the trend line to the recentimpedance scores, and/or the amount of time in the future when the trendline is predicted to reach the threshold. For example, a high R squarevalue for fitting the trend line to the recent impedance scores and/orthe trend line crossing the threshold in the near future are indicativeof a high probability. A low R square value indicating a poor fit of thetrend line, and/or an estimate of the trend line crossing the thresholdin the far future are indicative of a low probability.

At 116, the indication of accumulation of lung fluid is presented on adisplay and/or transmitted as an alert (e.g., a phone call, an email, apop-up message presented on a display).

The indication, optionally the impedance score, may be presented as apoint on a graph, optionally within a graphical user interface (GUI)presented on the display.

The graph includes a time axis (e.g., x-axis) indicative of the time atwhich the indication was obtained (e.g., impedance value measured), andan indication axis (e.g., y-axis) indicative of the value of theindication (e.g., value of the impedance score).

Points are plotted as the patient is monitored, optionally as impedancevalues are measured over time.

The computed trend line may be plotted within the graph on the GUI. Theextension of the trend line may be presented within the graph. Thefuture time at which the extension reaches and/or crosses the thresholdmay be indicated within the GUI. The computed probability of impendingaccumulation of clinically significant amount of fluid may be presentedwithin the GUI.

Alternatively or additionally, the graph includes a baseline impedancevalue (e.g., impedance score) measured for the patient at a statedetermined to be clinically insignificant for lung fluid. The value ofthe impedance may be monitored by computing subsequent current impedancevalues. Change in the current impedance value relative to the baselineimpedance value above a threshold may be indicative of accumulation (orclose to accumulation) of clinically significant amount of lung fluid.

Optionally, an alert is generated when a set of rules is met, indicatingimpending accumulation of clinically significant amount of lung fluid,for example, when the computed probability of prediction of accumulationof clinically significant amount of fluid is above a thresholdindicating high risk and/or when the trend line is heading in adirection towards a threshold denoting accumulation of clinicallysignificant amount of fluid. Alternatively or additionally, the alert isgenerated when an estimated amount of lung fluid is sensed, for example,according to a threshold and/or range. The alert may be transmitted, forexample, to a mobile device (e.g., of a health provider) and/or to amonitoring server (e.g., nurses' station), for example, as a pop-up boxappearing on the screen with a text message indicating risk of impendingaccumulation of fluid, an email, a phone call, and/or a flashing lightappearing within the GUI presenting the graph.

At 117, one or more additional features may be executed based on thecomputed impedance. The same electrodes and/or tube located within theesophagus may perform one or more additional features, in addition tothe estimation of the amount of lung fluid. The additional features maybe executed in parallel to the estimation of the amount of lung fluid,and/or sequentially in reference to the estimation of the amount of lungfluid.

Exemplary additional features include one or more of:

-   -   Estimating a level of fluid within the digestive system based on        an analysis of the applied alternating current and measured        voltage drop. The enteral feeding rate may be automatically        adjusted according to the estimated fluid level, for example, to        prevent reflux. Additional details of exemplary systems and/or        methods for estimating fluid levels based on impedance        measurements computed based on electrode(s) located on a tube        positioned within the esophagus may be found with reference to        International Patent Application No. IL2015/051156, by the same        inventors of the present application.    -   Monitoring a position of the tube within the digestive system        based on an analysis of the applied alternating current and        measured voltage drop. For example, to detect when the tube        moves out of the correct position. Additional details of        exemplary systems and/or methods for monitoring the position of        a tube based on impedance measurements computed based on        electrode(s) located on a tube positioned within the esophagus        may be found with reference to U.S. Pat. No. 9,713,579, by the        same inventors of the present application.    -   Detecting a gastric reflux event based on an analysis of the        applied alternating current and measured voltage drop. For        example, to stop enteral feeding. Optionally, when a gastric        reflux event is detected, the estimation of lung fluid may be        stopped and/or adjusted to account for the gastric reflux event,        for example, by subtracting the computed impedance value        (denoting total impedance due to lung fluid and reflux) from the        estimated impedance value due to the presence of fluid in the        esophagus due to the reflux. When no gastric reflux event is        detected, the measured impedance may be assumed to be an        indication of lung fluid without interference effects due to the        presence of fluid within the esophagus (i.e., the reflux).        Additional details of exemplary systems and/or methods for        detecting reflux event based on impedance measurements computed        based on electrode(s) located on a tube positioned within the        esophagus may be found with reference to International Patent        Application No. IL2017/050634, by the same inventors of the        present application.    -   Estimate functionality of lung(s) according to a correlation        between impedance values and lung function, and/or a correlation        between lung fluid and lung function. As lung fluid increases,        the functionality of the lungs decreases. Functionality of the        lungs may be for example, in terms of oxygen and carbon dioxide        exchange, and/or air volume capacity of the lungs. Oxygen and        carbon dioxide exchange is decreased due to the amount of tissue        available to perform the exchange, since fluid filled tissue        (i.e., pulmonary edema) cannot perform such exchange.        Alternatively or additionally, the lung may be compressed from        external fluid (e.g. pulmonary effusion) which reduces the        volume of air capacity of the lung, reducing lung efficiency.        The estimate of lung fluid (e.g., amount of fluid, change        relative to a baseline) may be correlated to lung function, for        example, according to a graph and/or function, which may be        empirically measured and/or computed based on mathematical        models. The estimated lung function may be computed as a change        relative an initial baseline (e.g., 100%). For example, a        certain increase in lung fluid may correspond to a 10% decrease        in lung function. In another example, a 15% decrease in        impedance may correspond to a 5% decrease in lung function.

At 118, acts 106-117 are iterated over time as part of the process ofmonitoring the patient for accumulation of clinically significant amountof lung fluid. Each iteration generates a current (i.e., real-time)impedance value and/or impedance score indicative of the current amountof lung fluid. The impedance values and/or scores may be plotted aspoints on the graph. The trend line may be dynamically computedaccording to the most recent points on the graph, for example, accordingto a sliding window. The GUI may be dynamically updated as new pointsare plotted and/or as the trend line and/or extension of the trend lineare dynamically updated based on the sliding window.

The monitoring may continue for example, as long as the tube is in usefor other purposes, for example, for enteral feeding of the patientand/or for draining excess fluid from the stomach of the patient. Forexample, monitoring for accumulation of lung fluid of an intubatedpatient being enterally fed by an enteral feeding over a period of 72hours.

Reference is now made to FIG. 11 , which is a schematic of an exemplarygraph 1102 presented on a display indicative of the sensed lung fluid,in accordance with some embodiments of the present invention. Graph 1102presents a curve indicative of the sensed fluid for a left lung 1104 anda right lung 1106. Curves 1104 1106 are plotted along an impedance scoreaxis 1108 (along the y-axis) as a function of time 1110 (along thex-axis). Curves 1104 and 1106 are dynamically updated in real time, asnew impedance values are computed.

The impedance score is computed based on the complex impedance value.The impedance score may be computed, for example, as the vector lengthof a vector representation of the complex impedance value, the value ofthe real component of the complex impedance value, and/or the value ofthe imaginary component of the complex impedance value. The impedancescore may be computed as an aggregation of multiple sub-impedance scoreseach computed for an impedance value measured at a certain AC frequency.Alternatively or additionally, the impedance score may be computed as anaggregation of multiple sub-impedance scores each computed for adistinct pair of electrodes, when the feeding tube includes multipleintra-body electrodes and/or when multiple extracorporeal electrodes arepositioned on the skin of the patient.

Graph 1102 includes a normal threshold 1112 denoting a lung withoutfluid, and/or with a normal amount of fluid, and/or with a clinicallyinsignificant amount of fluid, and include a clinically significantamount of lung fluid threshold 1114 denoting a lung with a clinicallysignificant amount of fluid. A region 1116 between thresholds 1112 and1114 denotes a lung that is at impending risk of accumulating aclinically significant amount of fluid, but is currently determined asbeing normal or having a clinically insignificant amount of fluid.Thresholds 1112 and 1114 correspond to thresholds 1010 and 1012described with reference to FIG. 10 , which are adjusted according tothe method used to convert the impedance value to an impedance score.

A trend indication 1118 is computed and plotted on graph 1102, forexample, as a trend line. The trend line 1118 may be dynamicallycomputed and adjusted, for example, based on a sliding window on arecent time interval. Trend line 1118 may be computed as a line that isbest fitted to the plotted impedance scores according to a least squarefit.

Optionally, trend line 1118 is extrapolated to predict a risk ofimpending accumulation of clinically significant amount of lung fluid.Trend line 1118 may be extended past the last plotted point according tothe most recent impedance measurement. The extension may be for apredefined time interval, for example, the next 30 minutes, 60 minutes,120 minutes, 6 hours, 12 hours, or 24 hours, or other values. Anextension that falls below threshold 1114 is indicative that the patientis trending towards accumulating a clinically significant amount offluid in the lung(s).

Various embodiments and aspects of the systems, methods, apparatus,and/or code instructions delineated hereinabove and as claimed in theclaims section below find experimental support in the following example.

EXAMPLE

Reference is now made to the following example, which together with theabove descriptions illustrates some implementations of the systems,methods, apparatus, and/or code instructions described herein, in a nonlimiting fashion.

An experimental set-up for sensing lung fluid based on at least oneintra-body sensor positioned in proximity and/or in contract with theLES is now described.

An intra-body sensor is positioned in proximity to and/or in contactwith the LES within the esophagus of organs extracted from an animal.Three clips representing extracorporeal electrode(s) were attached to alower lobe of a left lung at locations denoted as LL1 (within the upperportion of the lung), LL2 (within the middle portion of the lung), andLL3 (within the lower portion of the lung).

A first set of baseline impedance measurements were obtained by applyingone or more alternating currents and measuring the voltage between eachelectrode at locations LL1-LL3 and the intra-body electrode. Thebaseline impedance values were converted to an impedance score,representing a relative initial real number. The baseline impedancescore of the highest impedances at LL2 and LL3 was set to 1000. Thebaseline impedance score of LL1 was set relative to the baseline scoresof LL2 and LL3 as 850.

Fluid was administered into the lung three times:

-   -   40 cc (cubic centimeters) were injected close to the electrode        at location LL2.    -   40 cc (cubic centimeters) were injected close to the electrode        location LL3.    -   10 cc of fluid was poured into the lung.

Impedance values were computed after each administration of fluid, withrespect to each electrode, and converted to impedance scoresrepresenting a value relative to the baseline of 1000.

After a time interval of 2-3 minutes, impedance values were computedwith respect to each electrode, and converted to impedance scoresrepresenting a value relative to the baseline of 1000.

The results are presented in the table below:

40 cc 40 cc Poured Waited Base- close close 10 cc 2-3 line to LL2 to LL3into lung minutes LL1 (upper) 850 700-750 650-700 600 400 LL2 (middle)1000 750 700-760 800 400 LL3 (lower) 1000 1000 590-610 410 380-350

The experimental results illustrate that impedance values measured byintra-corporeal electrode(s) positioned within the esophagus and/orstomach in proximity to and/or in contact with the LES and by one ormore extracorporeal electrode(s) optionally positioned in proximity tothe lung(s) provide an indication of lung fluid, optionally anindication of clinically significant amount of lung fluid.

Alternatively or additionally, the above values may be indicative oflung function, where 1000 denotes a baseline, and values below 1000indicate a corresponding decrease in lung function.

Reference is now made to FIG. 12 , which is a schematic depicting anexemplary computed lung function and/or lung fluid map for presentationon a display of a client terminal (e.g., within a GUI), in accordancewith some embodiments of the present invention. The map includes, forone or more anatomical locations 1302 (e.g., lung lobes) indications1304 of corresponding impedance scores relative to a baseline, where thebaseline is indicative of normal or an initial state of the patientbeing monitored. Value below the baseline are indicative of a decreasein lung function and/or an increase in lung fluid, according to theselected mapping between impedance values and lung function and/orimpedance values and lung fluid.

The map may include numerical values of the relative impedance scoresand/or functional values and/or change in lung fluid corresponding toanatomical locations, and/or color coding of the anatomical locationsaccording to the scores and/or values and/or change in lung fluid and/ora graph indicative the values. The map visually identifies which areasof the lung are experiencing a relative decrease in function and/or anincrease in lung fluid.

For example, as shown in FIG. 12 , indications 1304 include a colorcoded bar graph, where each bar corresponds to a different anatomicallocation of the lung(s), and colors are indicative of severity, forexample, green is indicative of normal and/or no significant change frombaseline, orange is indicative of mild severity and/or not verysignificant change from baseline, and red is indicative of high severityand/or significant change from baseline.

The descriptions of the various embodiments of the present inventionhave been presented for purposes of illustration, but are not intendedto be exhaustive or limited to the embodiments disclosed. Manymodifications and variations will be apparent to those of ordinary skillin the art without departing from the scope and spirit of the describedembodiments. The terminology used herein was chosen to best explain theprinciples of the embodiments, the practical application or technicalimprovement over technologies found in the marketplace, or to enableothers of ordinary skill in the art to understand the embodimentsdisclosed herein.

It is expected that during the life of a patent maturing from thisapplication many relevant sensors and electrodes will be developed andthe scope of the terms sensor and electrode is intended to include allsuch new technologies a priori.

As used herein the term “about” refers to ±10%. The terms “comprises”,“comprising”, “includes”, “including”, “having” and their conjugatesmean “including but not limited to”. This term encompasses the terms“consisting of” and “consisting essentially of”.

The phrase “consisting essentially of” means that the composition ormethod may include additional ingredients and/or steps, but only if theadditional ingredients and/or steps do not materially alter the basicand novel characteristics of the claimed composition or method.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

The word “exemplary” is used herein to mean “serving as an example,instance or illustration”. Any embodiment described as “exemplary” isnot necessarily to be construed as preferred or advantageous over otherembodiments and/or to exclude the incorporation of features from otherembodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features unless such features conflict.

Throughout this application, various embodiments of this invention maybe presented in a range format. It should be understood that thedescription in range format is merely for convenience and brevity andshould not be construed as an inflexible limitation on the scope of theinvention. Accordingly, the description of a range should be consideredto have specifically disclosed all the possible subranges as well asindividual numerical values within that range. For example, descriptionof a range such as from 1 to 6 should be considered to have specificallydisclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numberswithin that range, for example, 1, 2, 3, 4, 5, and 6. This appliesregardless of the breadth of the range.

Whenever a numerical range is indicated herein, it is meant to includeany cited numeral (fractional or integral) within the indicated range.The phrases “ranging/ranges between” a first indicate number and asecond indicate number and “ranging/ranges from” a first indicate number“to” a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numerals there between.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

It is the intent of the applicant(s) that all publications, patents andpatent applications referred to in this specification are to beincorporated in their entirety by reference into the specification, asif each individual publication, patent or patent application wasspecifically and individually noted when referenced that it is to beincorporated herein by reference. In addition, citation oridentification of any reference in this application shall not beconstrued as an admission that such reference is available as prior artto the present invention. To the extent that section headings are used,they should not be construed as necessarily limiting. In addition, anypriority document(s) of this application is/are hereby incorporatedherein by reference in its/their entirety.

What is claimed is:
 1. A system for monitoring a subject, comprising: afeeding tube; a first electrode array comprising a plurality of spacedapart electrodes disposed along a length of the feeding tube; a secondelectrode array comprising a plurality of spaced apart electrodes, eachelectrode sized and shaped for contacting a surface of a skin of thoraxof a subject; at least one processor executing a code for: measuring aplurality of impedance values computed between the plurality ofelectrodes of the first electrode array and the plurality of electrodesof the second electrode array; and computing likelihood of a medicalstate of the subject according to an analysis of the plurality ofimpedance values.
 2. The system of claim 1, further comprising code forgenerating a tomographical impedance map of fluid in a lung according tothe plurality of impedance values.
 3. The system of claim 1, furthercomprising code for generating a 3D image of fluid in the lung accordingto the plurality of impedance values.
 4. The system of claim 1, whereineach of the first electrode array and the second electrode arrayincludes at least 5 electrodes.
 5. The system of claim 1, wherein whenthe feeding tube is in use, the first electrode array and the secondelectrode array face each other.
 6. The system of claim 1, wherein whenthe feeding tube is in use, the first electrode array and the secondelectrode array arranged for sandwiching a lung of the subject.
 7. Thesystem of claim 1, further comprising code for sweeping differentfrequencies between the first electrode array and the second electrodearray for obtaining the plurality of impedance values, and aggregatingthe plurality of impedance values for computing the likelihood of themedical state.
 8. The system of claim 1, wherein the plurality ofimpedance values are obtained for each anatomical region of a pluralityof different anatomical regions of a lung of the subject, the differentanatomical regions corresponding to different locations of the firstelectrode array and the second electrode array.
 9. The system of claim8, wherein the likelihood of the medical state is computed according toan analysis of the plurality of impedance values for the plurality ofdifferent anatomical regions of the lung of the subject.
 10. The systemof claim 8, further comprising code for generating a map according tothe plurality of impedance values obtained from each anatomical regionof the plurality of different anatomical regions.
 11. The system ofclaim 8, further comprising code for differentiating between the medicalstate of pulmonary edema and pleural effusion according to the analysisindicating at least one of (i) impedance values that are relativelylower at electrodes at positions corresponding to at least one lobeindicative of pulmonary edema at the at least one lobe, and (ii)impedance values that are relatively lower at a base of a lung butrelatively constant elsewhere are indicative of pulmonary effusion. 12.The system of claim 8, further comprising code for sweeping differentfrequencies between the first electrode array and the second electrodearray for obtaining the plurality of impedance values for eachanatomical region of the plurality of anatomical regions.
 13. The systemof claim 1, wherein the medical state comprises pleural effusion. 14.The system of claim 1, wherein the first electrode array and the secondelectrode array are positioned for avoiding passing current through aheart of the subject.
 15. The system of claim 1, further comprising codefor (1) selecting a combination including a selected frequency spectrumof an alternating current and a selected electrode pair including the afirst electrode from the first electrode array and a second electrodefrom the second electrode array, wherein the selected electrode pairdenotes a respective selected impedance sensor; (2) compute an impedancevalue according to voltage over the respective selected impedance sensorand according to the alternating current applied at the selectedfrequency spectrum by the respective selected impedance sensor; (3)compute a sub-impedance score according to the computed impedance value;(4) iterate (1), (2), and (3), wherein for each iteration anothercombination is selected that includes an electrode pair that has notbeen previously selected in previous iterations, the electrode pairincludes one electrode of the first electrode array and one electrode ofthe second electrode array, and at least another selected frequency ofthe alternating current applied by the respective selected impedancesensor and used to obtain the impedance value, for computing theplurality of impedance scores at a plurality of selected frequencies ofthe alternating current applied by the respective selected impedancesensors.
 16. The system of claim 1, wherein the second electrode arrayis for placement along the thorax in proximity to a first lung of thesubject, and further comprising a third electrode array for placementalong the thorax in proximity to a second lung of the subject, and codefor analyzing the plurality of impedance values obtained between thefirst electrode array and the second electrode array, and between thefirst electrode array and the third electrode array, for differentiatingbetween lung fluid processes that affect both lungs equally from lungfluid processes that affect only one lung.
 17. The system of claim 1,wherein the second electrode array is for placement along the thorax inproximity to a first lung of the subject, and further comprising a thirdelectrode array for placement along the thorax in proximity to a secondlung of the subject, and code for analyzing the plurality of impedancevalues obtained between the first electrode array and the secondelectrode array, and between the first electrode array and the thirdelectrode array, for determining fluid level in the first lung and thesecond lung.
 18. A method for monitoring a subject, comprising:measuring a plurality of impedance values computed between a pluralityof spaced apart electrodes of a first electrode array that are disposedalong a length of a feeding tube and a plurality of spaced apartelectrodes of a second electrode array , each electrode of the secondelectrode array is sized and shaped for contacting a surface of a skinof thorax of a subject, while the feeding tube is in use; and computinglikelihood of a medical state of the subject according to an analysis ofthe plurality of impedance values.
 19. A computer program product formonitoring a subject, comprising: a non-transitory memory having storedthereon a code which, when executed by at least one hardware processorof a computing device, while a feeding tube is in use, cause the atleast one hardware processor to: measure a plurality of impedance valuescomputed between a plurality of spaced apart electrodes of a firstelectrode array that are disposed along a length of the feeding tube anda plurality of spaced apart electrodes of a second electrode array ,each electrode of the second electrode array is sized and shaped forcontacting a surface of a skin of thorax of a subject; and computelikelihood of a medical state of the subject according to an analysis ofthe plurality of impedance values.